The Role Of Annexin A3 In Regulating Breast Cancer And The Establishment Of Breast Cancer PDX Model

In recent years, breast cancer has become the most common malignancy in women, of which morbidity and mortality are at a high level, it is a serious threat to women’s health. Although in recent years with the deepening of research, breast cancer diagnosis and treatment have made great progress, but it is still often observed that some of the existing breast cancer treatment (radiotherapy,chemotherapy, hormone therapy) are tolerant or no response. This reality forces us to continue to find new treatments and targets. Cancer stem cells (CSCs) are the theory put forward in recent years. The theory holds that CSCs are a group of cells with self-renewal and differentiation abilities in the tumor, and play a decisive role in tumor formation and growth. For their strong tolerance to traditional therapy,CSCs are considered as the root cause of cancer recurrence and metastasis. At the same time breast cancer research relies heavily on animal models, among which breast cancer patients-derived xenograft (PDX) tumor model is the use of patient-derived breast tumor tissues established in situ in immunodeficiency mice,can reflect the patient’s information to a large extent which has highly application value. In this study, the regulation mechanism of breast cancer stem cells and the clinical application were studied, and the establishment method of PDX model was optimized. The main contents were as follows:1, We found that Annexin A3 (ANXA3) in breast cancer tissue expression is upregulated, and with the prognosis of patients with a negative correlation. In a further functional experiment, we found that interfering the expression of ANXA3 with shRNA in breast cancer cells inhibits cell invasion but promotes cell proliferation. In further studies, we found that this effect of ANXA3 was mediated by regulation of transformation between epithelial-like and mesenchymal-like breast cancer stem cells (BCSCs). Through transcriptional analysis, we found that this modulation is caused by the effect of NF-κB pathway. Finally, we found that interfering with ANXA3 can promote the accumulation of chemotherapy drugs in cancer cells to improve the efficacy of chemotherapy reagents, animal treatment experiments showed knockdown of ANXA3 expression combine with the application of chemotherapy drugs, can significantly inhibit the transfer and growth of breast cancer simultaneously.2, We have optimized the existed protocol of breast cancer PDX model establishment, improved the success rate, and successfully established twelve different subtypes of Chinese breast cancer patients based PDX model. The results of immunohistochemical staining showed that the tissue morphology and molecular phenotypes were consistent with the parental tissue, which proved that the model was stable and passaged, and it could maintain the original pathological information of the patients. Those models can be used in research of novel drug and new therapy development.